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• Bengtsen, Mads; Winje, Ivan Myhre; Eftestøl, Einar; Landskron, Johannes; Sun, Chengyi & Nygård, Kamilla Børve [Show all 10 contributors for this article] (2021). Comparing the epigenetic landscape in myonuclei purified with a PCM1 antibody from a fast/glycolytic and a slow/oxidative muscle. PLoS Genetics. ISSN 1553-7390. 17:e1009907(11). doi: 10.1371/journal.pgen.1009907. Full text in Research Archive Show summary

  Muscle cells have different phenotypes adapted to different usage, and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of the epigenetic landscape by ChIP-Seq in two muscle extremes, the fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where up to 60% of the nuclei can be of a different origin. Since cellular homogeneity is critical in epigenome-wide association studies we developed a new method for purifying skeletal muscle nuclei from whole tissue, based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labelling and a magnetic-assisted sorting approach, we were able to sort out myonuclei with 95% purity in muscles from mice, rats and humans. The sorting eliminated influence from the other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the differences in the functional properties of the two muscles, and revealed distinct regulatory programs involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles were also regulated by different sets of transcription factors; e.g. in soleus, binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SIX1 binding sites were found to be overrepresented. In addition, more novel transcription factors for muscle regulation such as members of the MAF family, ZFX and ZBTB14 were identified.

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• Aders, Eirin; Nygård, Kamilla Børve; Bengtsen, Mads & Gundersen, Kristian (2021). Uncovering epigenetic mechanisms behind muscle memory. Full text in Research Archive
• Dyhre, Benjamin; Bengtsen, Mads; Nygård, Kamilla Børve; Millay, Douglas P. & Eftestøl, Einar (2021). How does a reduced myonuclear number affect epigenetic regulation of muscle function? Full text in Research Archive
• Nygård, Kamilla Børve (2026). Exploring the function and enzymology of protein methylation in skeletal muscle. Universitetet i Oslo. Full text in Research Archive Show summary

  Protein methylation is a fundamental process in which a small chemical group (CH3) is added to proteins by enzymes called methyltransferases. These modifications play an important role in regulating and optimizing protein function. In skeletal muscle, several proteins are known to be methylated. However, for many of these, the functional relevance of the modification, as well as the responsible enzyme, remains elusive. This thesis therefore explores the biological role of these modifications and identifies the enzymes involved. A protein of particular interest is the motor protein myosin, which for several decades has been known to be methylated at several positions. In this work, we identify the enzyme responsible for methylating a site located near myosin´s ATP-binding region, suggesting a role in optimizing its activity. In addition, we show that METTL21C, an enzyme predominantly expressed in skeletal muscle, modifies the contractile protein fast myosin-binding protein C (fMyBPC). Notably, this modification appears to be restricted to certain muscle types. Taken together, the findings demonstrate that muscle-specific methyltransferases target functionally relevant muscle proteins, highlighting protein methylation as an important mechanism in regulating the contractile machinery, muscle specialization, and potentially disease.

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